Butyrate attenuates BCLX(L) expression in human fibroblasts and acts in synergy with ionizing radiation to induce apoptosis.
Ionizing radiation is a poor inducer of apoptosis in many cell types. In this study we investigated what effect the differentiation agent butyrate had on the cellular levels of the apoptosis regulators BCL2, BCLX(L) and BAX and on radiation-induced apoptosis. It was found that butyrate significantly lowered the level of the apoptosis antagonist BCLX(L) in a time- and dose-dependent manner in diploid human fibroblasts. The reduction of the level of BCLX(L) protein by butyrate correlated with an increased induction of apoptosis in cells irradiated with ionizing radiation. Butyrate also acted in synergy with ultraviolet (UV) light and cisplatin to induce apoptosis in human fibroblasts. Radiosensitization was obtained when butyrate was added before and/or after irradiation, although the combination of treatment both before and after irradiation was the most effective. Our results suggest that butyrate acts in synergy with ionizing radiation, UV light and cisplatin to induce apoptosis, perhaps by lowering the level of the apoptosis antagonist BCLX(L) in cells.
Chung
D H
DH
Department of Radiation Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor 48109-0936, USA.
Zhang
F
F
Chen
F
F
McLaughlin
W P
WP
Ljungman
M
M
D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D002087:Butyrates / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects / Q000528:radiation effects; D005347:Fibroblasts; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D011839:Radiation, Ionizing; D011838:Radiation-Sensitizing Agents; D016196:S Phase / Q000528:radiation effects; D013997:Time Factors; D014158:Transcription, Genetic; D014466:Ultraviolet Rays; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D002087:Butyrates; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011838:Radiation-Sensitizing Agents; D051020:bcl-X Protein; D002945:Cisplatin